PROJECT SUMMARY Our Small Business Innovation Research initiative is focused on offering novel, cost-effective clinical equipment and techniques that significantly impact and advance diagnostics and therapeutic monitoring of a variety of cancers. HyperE proposes to design and produce the first commercial-ready parahydrogen induced polarization (PHIP) instrument to facilitate the breakthrough of PHIP, an emerging enhanced MRI technique with major clinical potential for molecular imaging with new generation agents. In conjunction with MRI, PHIP amplifies the inherently low MRI signal enabling in vivo molecular imaging supported by hyperpolarized molecules that inform cellular composition and metabolism, critical factors for identification and tracking of cancer tissue. Commercial PHIP equipment to be coupled with MRI is not available at present. So far, exploration of this promising yet complex technology has been limited to a handful hyperpolarization/MRI research experts with the technical skill and facility to construct their own equipment. Our custom-built polarizer prototype at Cedars- Sinai has proven to set the benchmark in performance and resulted in valuable published PHIP experimental insight. Upon implementation of our innovative new design, the proposed instrument is not only expected to be state-of-the-art in functionality, flexibility, affordability, and usability, but also meet feasibility criteria for clinical use via access to new hyperpolarized molecules. Our HyperE Phase I proposal aims to produce turn-key research equipment for studying new metabolism and molecular targeting agents to better detect, characterize and track changes in cancer. Aim 1 of phase I: Build the first commercial-ready homogeneous/heterogeneous catalyst PHIP polarizer for research labs that reliably produces >20% polarization. Rationale ? a universal PHIP polarizer for multiple catalyst schemes is a completely new technology for basic science, as well as preclinical research. Aim 2 of phase I: Validate the polarizer functionality through comparison of the prototype design vis--vis the proposed two chamber design to assess hydrogenation performance and carbon polarization transfer. Rationale ? setting the framework for optimal carbon polarization, as well as precise comparative performance analysis will confirm the impact of the improved homogeneous magnetic field design. The ultimate goal (proposal phases II and III) is to evolve the design to commercially fabricate and provide a marketable product for under $300k for clinical utilization. We envision that our instrument design will not only represent a technological research innovation but open up completely new clinical imaging possibilities not available with current medical practice tools. This polarizer is projected to propel MRI combined with PHIP to play a major role in cancer detection and treatment control, addressing unmet needs and joining the ranks of PET and CT.